Encouraging News From Initial Covid-19 Prevalence Studies

Encouraging News From Initial Covid-19 Prevalence Studies

Encouraging News From Initial Covid-19 Prevalence Studies

Preliminary results from a growing number of antibody prevalence studies indicate that the Covid-19 virus has spread more widely and has a lower fatality rate than previously expected.

Stanford University School of Medicine

Between 48,000 and 81,000 residents in northern California had been infected by Covid-19 as of April 1. This is more than 50 times higher than the official count at the time of 956 cases, according to a prevalence study conducted by researchers at the Stanford University School of Medicine. The Stanford study was based on 3,300 blood samples that were taken from volunteers in Santa Clara County in early April and tested for antibodies to Covid-19. Based on 100 estimated Covid-19 deaths in the county and 48,000-81,000 cases, the Stanford researchers estimate an infection fatality rate of between 0.1% and 0.2%. The Stanford research team is conducting similar antibody prevalence studies in Los Angeles County as well as a national study of 10,000 athletes and employees from 27 Major League Baseball teams. “We’re hoping that once we get accurate numbers in place, we’ll be able to quell the fear that’s out there,” said Jay Bhattacharya, who holds an MD and PhD in economics from Stanford University.

Massachusetts General Hospital

Pathologists with Massachusetts General Hospital have found that Covid-19 is far more widespread than the official case count in the Boston area. MGH set up a testing tent in the middle of Bellingham Square in Chelsea, MA, in mid-April and took finger-prick blood samples from 200 healthy-looking residents. Samples were tested using a ten-minute rapid test made by BioMedomics. The device hasn’t yet been approved by the FDA, but MGH has validated the test. The researchers found that one third of study participants (64 people) had Covid-19 antibodies. “The bad news is that there’s a raging epidemic in Chelsea, and many people walking on the street don’t know that they’re carrying the virus, according to John Iafrate, MD, PhD, Vice Chairman of MGH’s pathology department and the study’s principal investigator. “On the good-news side, it suggests that Chelsea has made its way through a good part of the epidemic.”

University of Bonn

Preliminary results from a study focused on a small German town named Gangelt indicate that about 15% of its population has been infected Covid-19. Located near the border with the Netherlands, Gangelt has been dubbed “Germany’s Wuhan” because it was hard hit by Covid-19 after a February 15 carnival celebration drew thousands to the town (population: 12,529). In early April, researchers from the University of Bonn performed antibody testing on 1,000 people from the town and found that 15% of the population had been infected and the process towards herd immunity is already taking place. The mortality rate among the studied population was 0.37%, five times lower than that currently registered in Germany, which corroborates the suspicions that the number of infected is much higher than the diagnosed. “It is important to obtain this data in order to make sure that decisions are taken based on facts rather than assumptions,” according to Hendrik Streeck, MD, PhD, Head of the Institute of Virology and Institute for HIV Research, University Hospital Bonn.

Spotlight Interview with ARUP Laboratories’ Julio Delgado

Spotlight Interview with ARUP Laboratories’ Julio Delgado

Spotlight Interview with ARUP Laboratories’ Julio Delgado

ARUP Laboratories (Salt Lake City) began PCR testing for SARS-CoV-2 – the
virus that causes Covid-19 – March 12 and is currently able to run about 3,000 tests per day. Due to supply constraints, ARUP announced March 16 that it would focus SARS-CoV-2 PCR testing on clients within the state of Utah. Laboratory Economics recently spoke with Chief Medical Officer Julio Delgado, MD, about the pandemic and what ARUP is doing to ramp up testing.

Is ARUP’s Covid-19 test volume primarily for symptomatic hospital patients?
The majority of the samples we are doing are from symptomatic patients and healthcare workers. We also are supporting drive-through testing. (As of April 12, Utah had tested more than 45,000 residents and had 2,207 confirmed cases of Covid-19 and 18 deaths.)

Is your lab experiencing any shortage of test supplies, reagents or sample collection swabs?
Everything has been a challenge, every single aspect of this. Anything we need to do this test we have run into supply chain issues—collection devices, media for transport, reagents, instrumentation, everything. We can only promise five days ahead of time in terms of our capacity. It was really bad in the beginning, and it’s a little better now, but it’s still a challenge. We don’t have long term commitments from any vendors for supplies.

Are most coronavirus tests being ordered in conjunction with a respiratory virus panel?

We saw that initially, but that has decreased. It started with a one-to-one ratio, then it went to two-to-one, five-to-one—now it’s approximately twenty-to-one. The two tests are run on the same instrumentation. In Utah, clinicians are focused primarily on Covid-19 as we move out of the winter.

How many coronavirus tests can your lab perform per day?
We have capacity for about 3,000 a day. The challenge is that because we cannot secure a continuous supply chain, we can only take so many samples.

Are test orders exceeding capacity?
Since we closed the national offering, we have managed much better. We got completely flooded—in the beginning we had thousands of orders coming in. I believe we made the right decision for patient care to stop testing nationally. Of those initial national requests, we processed several
internally, and we sent some to commercial reference laboratories, but they were backlogged, too. We finally were able to report everything, but it took a long time.

Does ARUP currently perform an antibody test for Covid-19?
Not today, but we are working on it. We are hoping to have it ready in a week or two. This will be used for convalescent individuals and people who think they may have had the virus. This will help determine if someone has developed immunity and whether they can go back to work.

Has ARUP seen a decline in non-Covid-19 testing?
Yes, absolutely. With 80% of the country at home, people are not going to medical checkups, elective surgeries are not being done. Non-Covid testing is down at least 25% and decreasing.

Which instrument system does ARUP use to perform Covid-19 testing?
We have been using Hologic instruments [Panther Fusion]. We are getting ready to start using Roche cobas, so we will be using both. We hope to be able to run more tests, beyond 3,000, but that depends on the supply chain.

What precautions are you taking to protect lab employees from getting the virus?
We are doing everything dictated by the CDC. So far, we have been lucky—none of our virology lab workers have contracted the virus as far as I know. Those who are running the tests are using N95 masks, face shields, gowns. So far, we have had enough personal protective equipment, but we have not been able to replenish it at the same rate we were before. The lab staff are keeping at least six feet apart.

Could the warmer more humid weather in the spring/summer slow down the spread of Covid-19?
I don’t know. What’s your turnaround time for Covid-19 testing results?
We are promising within three to four days, but in most cases it’s two days. Hologic is a random-access instrument, which allows us to incorporate testing and move things ahead – that way we can prioritize testing for very sick patients.

Are you doing any rapid testing?
We have two BioFire instruments in the hospital system. They do one test at a time, and it takes about 45 minutes. We are using them judiciously in very critical and emergency situations. We also have several Abbott ID NOW instruments, and we have ordered tests, but areas with critical needs are being prioritized. We are on the list, and at some point we will get them.

Do you believe that surveillance testing of non-symptomatic people for Covid-19 is needed?
I believe so, but with the limitations of the supply chain, we aren’t able to do that. Right now, testing is all reactive. Surveillance testing would give us a better understanding of the epidemiology and the curves that each of the states will go through.

Spotlight Interview With Viracor’s Steven Kleiboeker

Spotlight Interview With Viracor’s Steven Kleiboeker

Spotlight Interview With Viracor’s Steven Kleiboeker

 Viracor Eurofins Laboratories (Lee’s Summit, MO) is a specialty laboratory focused on infectious disease, immunology and allergy testing for immunocompromised and critical patients. Viracor is a 100% subsidiary of Eurofins Scientific (Luxembourg). Under the FDA’s Emergency Use Authorization Guidance, Viracor was one of the first private labs to introduce a laboratory-developed test (LDT) for Covid-19. Laboratory Economics recently spoke with Viracor’s Steven Kleiboeker, PhD, Vice President of Research and Development.

Describe the current status of Viracor’s Covid-19 testing?
We started Covid-19 testing on March 13 using our unique assay design which included EasyMag specimen nucleic acid extraction and Thermo’s ABI 7500 analyzer and reagents. Our initial capacity was 1,000 tests per day with turnaround time within 24 hours of specimen receipt. We quickly
ramped to 2,000+ tests per day with 2-3 day TAT. Our sister lab in Alabama, Diatherix Eurofins, is also performing Covid-19 testing with capacity of 2,000 – 3,000 tests per day.

A large percentage of those tests are processed within 24 hours. However, due to a small backlog, unprecedented demand, pressures on our supply chain, and shipping delays (some of which are related to specimen quality), our turnaround time for some clients has been pushed beyond what we normally experience. At most, we are looking at a 2-3 day TAT.

Ultimately, we expect to get turnaround times across-the-board back down below 24 hours, but right now, the greatest need is for increased testing capacity. Both labs are running 24/7 at full capacity and we still can’t meet the demand for testing. We have increased capacity by adding an additional platform (Abbott).

Are you encountering any supply shortages?
The supply chain is stretched and we’re doing all we can to stay half-a-step ahead. Specimen collection kits and swabs are a choke point. It’s hard to find the preferred universal transport media (UTM) collection kits, so we’re now looking at viral transport media (VTM) kits and phosphate buffered saline (PBS) as an alternative to keep specimen swabs moist during transport. Beyond swab and sputum samples, we are also exploring other specimen types.

Why did Viracor and Diatherix developed their own assays?
Instead of developing a single test, Viracor Eurofins and our sister lab, Eurofins Diatherix, leveraged our unique capabilities, techniques and equipment to develop a proprietary, molecular SARS-CoV-2 assay for Covid-19. This approach allowed each lab to go-to-market faster and because of the anticipated supply chain issues, it also allowed us to stratify risk across suppliers.

Diatherix uses a proprietary technology, TEM-PCR (Target Enriched Multiplex Polymerase Chain Reaction) for precise detection of infectious diseases at high levels of sensitivity and specificity, and at very short turnaround times. It’s also a cost-effective way to multiplex several different respiratory pathogens.

If requested, the Diatherix assay for Covid-19 can be combined with other respiratory tests, producing results highly comparable to a standalone Covid-19 test.

Are you seeing prices rise for gloves, collection kits and swabs as a result of the shortages?
While there is pricing variability in this space, my impression is that prices have not increased with increased demand.

Where are your Covid-19 test orders coming from?
We provide reference testing services to approximately 200 academic medical centers and hospitals and that’s where the orders are coming from. We’ve added 10-20 new clients in the past few weeks. Hospitals are sending samples to wherever they can get the test result the fastest, whether that’s a state public health lab or private lab.

Are most Covid-19 tests being ordered in conjunction with a respiratory virus panel?
The combination of a Covid-19 test and respiratory virus panel and/or flu test is necessary because 4-7% of cases have co-infections (simultaneous infection by two or more viruses).
Are you working on an antibody test for Covid-19?
Another Eurofins lab subsidiary, Boston Heart Diagnostics (BHD), has developed a Covid-19 antibody test that was launched in early April. The blood-based antibody test identifies people who were exposed and developed an immunity to Covid-19, but potentially had mild to no symptoms. This test—unlike the NP swab which determines active infection—is a crucial next step in fighting the spread of Covid-19. Antibody testing should be done at least 14 days after exposure. Viracor will also soon be introducing a Covid-19 antibody test.

Given the overwhelming demand in acute care settings, the test will be initially offered to hospitals nationwide. As capacity increases, we will begin testing less acute patient populations, eventually allowing those with immunity to get out of quarantine and back to work.

Initial capacity will be nearly 5,000 tests per day, or 200 results every hour. Hospitals along the east coast, including those in hot-spot areas, will have the option to courier specimens to BHD for results in just hours. Speed is crucial to helping first responders and healthcare providers assess their ability to be on the front lines. Once Viracor’s antibody assay is launched, we expect daily capacity to increase.

Are other test volumes declining because people are staying home/less doctor visits?
Testing not related to Covid-19 has declined overall for a variety of reasons—people are staying home, not wanting to put themselves at risk by going to the hospital, etc. However, if you look at some of our most critical tests, like viral load testing, antiviral drug resistance testing, and immunology testing, the volume is mostly unchanged.

What precautions are you taking to protect lab employees from getting the virus?

It’s incredibly important that our lab scientists stay healthy. We have about 150 lab employees at Viracor and all non-essential lab personnel that can work from home are doing so. We’ve made it clear that any employee with symptoms should stay home and we’re taking the temperature of every employee before they enter the lab.

Do you see any similarities when compared to past outbreaks like Swine Flu, Zika or Ebola?
This really is unprecedented and will be a serious public health issue for at least the next few months, not weeks.

Could the warmer more humid weather in the spring/summer slowdown the spread of Covid-19?
Other respiratory viruses have been most problematic in the colder months when more people are together in enclosed rooms. The warmer months may bring some relief, but won’t be the savior.

What signs would tell you that the worst is over from Covid-19 in the United States?
If cases stabilize or decline, that would certainly be a good sign. However, it could be due to warmer weather, social distancing or some other unknown factor. However, if any of those known (or unknown) factors reverse, or others come into play, we could certainly see another period of increasing cases.

More Testing Needed So Policy Makers Can Make Rational Decisions

More Testing Needed So Policy Makers Can Make Rational Decisions

More Testing Needed So Policy Makers Can Make Rational Decisions

Right now, sample collection kit shortages in the United States mean that Covid-19 testing has rightly been focused on the most severe symptomatic patients. But this is skewing our understanding of the virus and its true risks. And policy decisions that will have tremendous consequences are being made based on this incomplete data.

The Diamond Princess Case Study

An outbreak of Covid-19 on the Diamond Princess cruise ship was started by a single symptomatic passenger from Hong Kong who boarded the boat on January 20. He disembarked on January 25, and tested positive for the virus on February 1. This led to a quarantine of approximately 3,700 passengers and crew that began on February 3, 2020, and lasted for nearly four weeks at the Port of Yokohama, Japan. During the “quarantine,” the crew continued to prepare and deliver food, and health workers moved throughout the ship.

The Diamond Princess offers a real-life controlled experiment where 100% of passengers and crew were tested. It has everything all the other Covid-19 stats are currently lacking in order to accurately estimate the fatality rate for Covid-19: an undisputable numerator (10 deaths) and a complete 100% accounted for denominator (712 positive cases). The Diamond Princess provides a worst-case scenario where basically a bunch of older people were trapped in a large container with the virus for a month.

Here’s what the data from the Diamond Princess showed:

  • A total of 3,711 people were onboard (1,045 crew/2,666 passengers)
  • The overall median age was 58 and 33% were 70 or older.
  • Most of the passengers were from Japan (1,281) and the United States (416).
  • Most of the crew was from Philippines (531) and India (132).
  • 712 people (19.2%) tested positive for Covid-19, including 567 passengers and 145 crew members.
  • About half (46.5%) of those who tested positive showed no symptoms at their time of testing.
  • Ten people died from Covid-19.
  • All deaths were among passengers age 70 or older.
  • The case fatality rate was 1.4% (10 deaths/712 cases).

The Diamond Princess case study stands in sharp contrast to initial reports from the World Health Organization which wildly overestimated the global case fatality rate of Covid-19 to be 3.4%.

Applying the Diamond Princess’s infection rate of 19.2% and case fatality rate of 1.4% across the entire U.S. population of 330 million would lead to estimates of 63.4 million cases and 887,600 deaths.

However, the median age of passengers and crew on the Diamond Princess (58) was about 20 years higher than the median age of the U.S. population (38).

After adjusting for the age difference, John Ioannidis, MD, an epidemiologist and biostatistician at Stanford University, has calculated that a reasonable estimate for the fatality ratio in the general U.S. population falls in a range of 0.05% to 1%.

In a March 17 opinion piece for STAT, Ioannidis said that the huge range in potential case fatality ratios markedly affects how severe the pandemic is and what should be done. “A population-wide case fatality rate of 0.05% is lower than seasonal influenza [0.1%]. If that is the true rate, locking down the world with potentially tremendous social and financial consequences may be totally irrational.”

Ioannidis said that testing for Covid-19 should be conducted in a random sample of the population and repeated at regular time intervals to estimate the incidence of new infections. In the absence of data, prepare-for-the-worst reasoning leads to extreme measures of social distancing and lockdowns that may or may not work. “If we decide to jump off the cliff, we need some data to inform us about the rationale of such an action and the chances of landing somewhere safe,” wrote Ioannidis.

Link to Ioannidis article:
A fiasco in the making? As the coronavirus pandemic takes hold, we are making decisions without reliable data